The present invention provides a device and methods for detecting the presence of an analyte in a sample, more particularly to devices and methods for transdermal monitoring of an analyte. Methods for manufacturing the device are also disclosed.
The monitoring of certain analyte concentrations in the body enables early detection of health risks, and identifies the need for the introduction of therapeutic measures. One of the most commonly monitored analytes is glucose. The concentration of glucose in the blood is an important parameter which determines the appropriate dosages of insulin for diabetics. Various methods have been developed for monitoring glucose levels in the blood, including methods conducted in vivo. For example, an implantable fluorescence affinity hollow fiber sensor has been reported for the continuous transdermal monitoring of glucose in the blood (see, for example, Schultz et al., Analytical Chemistry Vol. 72, No. 17, pp. 4185-4192). The interiors of such hollow fiber sensors are packed with cross-linked dextran beads and fluorescently-tagged bio-reagents that display fluorescence changes with rising concentrations of glucose. Detection of the fluorescence is achieved extracorporeally (e.g., with an optical unit incorporating a laser and a photodetector) and is correlated with a concentration of glucose in the blood.
Implantable sensors currently require some form of surgery to place the implant under the skin because of the large size of the implant. The larger the implant, and the more exterior seams and sealing interfaces it has, the more likely that there will be an immunological response or infection. Infection is especially problematic for immuno-compromised patients or patients receiving immunosuppressive drugs.
In addition to undesirable immunological response, current implantable sensors lack long-term usefulness due to potential leakage and rupture at the assembly seams. Whether the device is assembled with mechanical O-rings or chemical adhesives, the seams are prone to failure in the liquid environment of a living organism. An example of a sensor requiring an O-ring seal is disclosed in U.S. Pat. No. 5,143,066. Other implantable devices, such as those disclosed in U.S. Pat. Nos. 5,756,115 and 5,814,449, rely on adhesives to seal their layers or ends together. Current implants generally consist of a tube or hollow fiber sealed at both ends with an adhesive. Accordingly, there is a need to develop implantable sensor devices that lack sealing surfaces and can be made in a wide variety of sizes, starting in the sub-micron range.
This invention provides an encapsulated, size-scalable sensor device that can be made small enough to implant with only a small incision or, more preferably, with a needle. If desired, multiple devices can be implanted at one site to increase the signal strength. Additionally, the encapsulation membrane is “seamless” in that it forms a contiguous surrounding for the device that lacks joining seams or edges.
Unlike mechanically sealed devices which rely on rubber-type O-rings or adhesives to seal their parts together, the present device lacks edges or sealing interfaces. This elimination of joining seams or edges provides enhanced rupture resistance and decreased chance of immunological response. Additionally, the smooth exterior aids in ease of implantation. The device is also significantly easier to manufacture because the various components do not require manual assembly and sealing.